AMP-activated protein kinase (AMPK) is decreased in the mouse brain during experimental cerebral malaria

Area of Science:

• Neuroscience
• Infectious Diseases
• Biochemistry

Background:

• Cerebral malaria (CM) is a severe neurological complication of Plasmodium infection, leading to coma and death.
• Adenosine 5 -monophosphate-activated protein kinase (AMPK) is a critical metabolic regulator involved in cellular energy homeostasis.
• Understanding AMPK's role in CM pathogenesis is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the status and role of AMPK in a mouse model of cerebral malaria.
• To determine if AMPK gene expression and protein phosphorylation are altered during CM.

Main Methods:

• Utilized a C57BL/6 mouse model infected with Plasmodium berghei ANKA to induce CM.
• Assessed gene expression of AMPK subunits (Prkaa1, Prkaa2) in brain tissue.
• Quantified protein levels of phosphorylated AMPK (p-AMPK) and total AMPK, as well as phosphorylated acetyl-CoA carboxylase (p-ACC) and total ACC.

Main Results:

• Demonstrated a statistically significant reduction in Prkaa1 and Prkaa2 gene expression in the brains of CM mice compared to controls.
• Observed a significant decrease in the ratio of phospho-AMPK/AMPK protein levels in CM mouse brains.
• Found no significant change in the phospho-ACC/ACC ratio, indicating specific alterations in AMPK activation.

Conclusions:

• AMPK is downregulated in the context of cerebral malaria.
• Reduced AMPK activity may contribute to neuronal cell death during CM.
• Targeting AMPK with activating drugs could offer neuroprotective adjunctive therapy for CM.